United States Drug Patent 4,078,071: Claim Scope, Expiration, and Antifungal Patent Landscape

U.S. Patent No. 4,078,071 covers substituted imidazole compounds, their antimicrobial acid-addition salts, topical pharmaceutical compositions, and methods for inhibiting fungi, bacteria, and protozoa. The central chemical genus is an imidazole attached to a substituted phenylthio or phenoxyalkyl structure. The patent issued in 1978 under the pre-URAA patent-term regime and expired no later than 1995, assuming the recorded issue date of March 7, 1978. It does not create current U.S. exclusivity for generic manufacturers or sponsors developing related imidazole antifungals.[1]

The patent is historically relevant because its claims encompass multiple substituted imidazole antifungal structures, including chlorinated and brominated phenylthio derivatives. Its present commercial value is primarily freedom-to-operate and prior-art relevance, not enforceable exclusivity.

What does U.S. Patent 4,078,071 cover?

The patent covers four principal subject-matter categories:

Chemical compounds.
Antimicrobial acid-addition salts.
Pharmaceutical and nonpharmaceutical compositions.
Methods of inhibiting fungi, bacteria, and protozoa.

The independent compound claim is claim 1. Claims 2 through 28 narrow the chemical genus through substituent, chain-length, halogen, sulfur, and positional limitations. Claim 35 separately protects a specifically identified compound.

Claims 29 through 31 cover compositions. Claims 32 through 34 cover antimicrobial methods.

Claim group	Subject matter	Principal limitations
Claims 1-28	Compounds and salts	Substituted imidazole derivatives with phenethyl, phenylpropyl, or styryl substituents
Claim 29	Antimicrobial composition	Effective amount plus suitable carrier
Claim 30	Pharmaceutical composition	Pharmaceutically acceptable, nontoxic carrier
Claim 31	Topical composition	0.1% to 10.0% active concentration
Claims 32-34	Methods	Applying or administering the compound to inhibit fungi, bacteria, or protozoa
Claim 35	Specific compound	1-[3-(2,6-dichlorophenylthio)-4-(4-chlorophenyl)butyl]imidazole and salts

What is the core chemical structure claimed by Patent 4,078,071?

The claimed compounds contain an imidazole ring connected to a substituted hydrocarbon chain bearing a second aryl group linked through oxygen or sulfur.

The broad structure includes:

R1 as phenethyl, phenylpropyl, or styryl;
R2 as phenyl, phenylalkyl, or phenylalkenyl;
X as oxygen or sulfur;
n as an integer from one to three;
independently substituted aryl rings;
lower alkyl, halogen, and trifluoromethyl substituents;
antimicrobial acid-addition salts.

The practical center of gravity is the sulfur-containing series. Claims 12 and 15 through 28 narrow the invention toward phenylthio compounds, particularly compounds having:

2,6-dichlorophenylthio substitution;
2,5-dichlorophenylthio substitution;
2,4-dichlorophenylthio substitution;
brominated phenylthio substitution;
a 4-chlorophenyl or 4-fluorophenyl terminus;
an imidazole ring at the terminal or near-terminal carbon chain position.

How broad is claim 1?

Claim 1 is a Markush genus claim. It does not protect only the named examples. It covers a potentially large number of compounds generated by selecting substituents within the listed alternatives.

Its breadth comes from five elements:

Three permitted R1 groups.
Three broad R2 categories.
Independent substitution of both phenyl rings.
Oxygen or sulfur as the linking atom.
Chain length of one to three carbon units.

The claim is materially narrower than a claim covering all substituted imidazoles because it requires the specified aryl-containing architecture. A compound lacking the required R1 or R2 structure would fall outside the literal scope of claim 1 even if it retained an imidazole ring and antimicrobial activity.

The claim also requires an antimicrobial acid-addition salt when the claimed subject is expressed as a salt. The free base and salt forms are treated within the claim language, but infringement analysis would depend on the precise claim construction and the commercial form being made, used, or sold.

Which claims protect the most commercially relevant compounds?

Claims 15 through 28 are the most commercially specific compound claims. They identify individual molecules with defined halogen patterns.

Claim	Claimed compound
15	2,6-Dichlorophenylthio and 4-chlorophenyl substituted butyl imidazole
16	2,5-Dichlorophenylthio and 4-chlorophenyl substituted butyl imidazole
17	2,4-Dichlorophenylthio and 4-chlorophenyl substituted butyl imidazole
18	2-Chlorophenylthio and 4-chlorophenyl substituted butyl imidazole
19	2,3-Dichlorophenylthio and 4-chlorophenyl substituted butyl imidazole
20	2-Bromophenylthio and 4-chlorophenyl substituted butyl imidazole
21	2,6-Dibromophenylthio and 4-chlorophenyl substituted butyl imidazole
22	2,4,6-Trichlorophenylthio and 4-fluorophenyl substituted butyl imidazole
23	2,6-Dichlorophenylthio and 4-fluorophenyl substituted butyl imidazole
24	2,6-Dichlorophenylthio and 4-chlorophenyl substituted but-3-enyl imidazole
25	2,6-Dichlorophenylthio and 4-chlorophenyl substituted pentyl imidazole
26	2,5-Dichlorophenylthio and 4-fluorophenyl substituted butyl imidazole
27	2,4,5-Trichlorophenylthio and 4-fluorophenyl substituted butyl imidazole
28	2,4,5-Trichlorophenylthio and 4-chlorophenyl substituted butyl imidazole
35	2,6-Dichlorophenylthio and 4-chlorophenyl substituted butyl imidazole with a different chain description

Claims 15 through 28 depend on claim 8, which requires R2 to be a halo-substituted phenyl or benzyl group. The dependency structure narrows the relevant compounds beyond the broad genus in claim 1.

What formulations are protected by U.S. Patent 4,078,071?

Claims 29 through 31 protect compositions containing a claimed compound or antimicrobial acid-addition salt.

Claim 29 is broad. It covers a composition useful against:

fungi;
bacteria;
protozoa.

The composition must include an effective amount of a covered compound and a suitable carrier. The claim is not restricted to human pharmaceutical use.

Claim 30 narrows the composition to pharmaceutical use and requires a pharmaceutically acceptable, nontoxic carrier.

Claim 31 narrows further to topical administration and specifies an active concentration of approximately 0.1% to 10.0% by weight.

The formulation claims do not identify a particular cream, ointment, gel, lotion, tablet, capsule, solvent system, preservative, penetration enhancer, or delivery device. Their scope therefore depends heavily on whether the active compound falls within the compound limitations and whether the carrier and concentration satisfy the claim language.

What method-of-use rights does the patent claim?

Claims 32 through 34 cover methods of inhibiting fungi, bacteria, or protozoa.

Claim 32 is the broad method claim. It covers applying an effective amount of the compound, salt, or composition to a host object containing or subject to attack by the target organism.

Claim 33 limits the method to topical administration.

Claim 34 covers oral or parenteral administration.

The method claims are not limited to a named disease, pathogen, anatomical site, patient population, or dosing schedule. They are framed around antimicrobial activity and administration route. Because the patent has expired, these claims do not create current method-of-use exclusivity.

When did U.S. Patent 4,078,071 expire?

The patent was granted under the pre-URAA term system, under which a U.S. utility patent generally ran for 17 years from grant rather than 20 years from the earliest effective nonprovisional filing date.[1,2]

Event	Date or status
U.S. patent number	4,078,071
Issue date	March 7, 1978
Original statutory term	17 years from grant
Latest ordinary expiration	March 7, 1995
Current enforceability	Expired
Current U.S. exclusivity	None

Any terminal disclaimer, maintenance-fee issue, disclaimer, or extraordinary adjustment could shorten the term, but none could extend the ordinary pre-URAA term beyond the applicable statutory period absent a specific extension. The patent is therefore not a current barrier to generic development.

What is the Orange Book status of Patent 4,078,071?

Patent 4,078,071 is not a current Orange Book exclusivity asset. The Orange Book lists patents submitted by approved drug applicants for approved drug products, including patents covering active ingredients, formulations, methods of use, and certain other listed categories.[3]

A patent can be historically related to an antimicrobial product without being listed in the current Orange Book. The patent’s age and expiration status eliminate any present Orange Book patent term. It also does not provide a current basis for a Paragraph IV certification against an unexpired listed patent.

Are there current Paragraph IV challenges involving this patent?

No current Paragraph IV challenge can create meaningful market risk from Patent 4,078,071 because the patent expired decades ago.

Paragraph IV litigation is relevant when an abbreviated new drug application applicant asserts that a listed patent is invalid, unenforceable, or not infringed. An expired patent cannot support a statutory period of generic delay or block FDA approval on the basis of remaining patent term.[2,3]

Historical litigation involving related imidazole products would need to be analyzed separately. Litigation against a different patent, a continuation, a formulation patent, or a method patent would not automatically affect the status of Patent 4,078,071.

Which companies are challenging Patent 4,078,071?

There is no current commercial challenge requiring a Paragraph IV strategy against this patent. The patent’s statutory term ended in the 1990s.

The relevant competitive parties today would instead include:

generic manufacturers developing related imidazole antifungals;
branded companies holding later formulation or delivery patents;
manufacturers supplying active pharmaceutical ingredients;
sponsors pursuing new topical or oral antifungal products.

Patent 4,078,071 may remain relevant as prior art in validity analysis for later patents. It can be cited against later claims directed to structurally similar imidazole thioethers, substituted aryl chains, or antimicrobial formulations.

How strong is the patent estate for the claimed compounds?

The historical estate was moderately broad at the compound level but limited at the product-system level.

Estate characteristic	Assessment
Core genus	Broad Markush coverage
Specific compounds	Numerous narrow species claims
Salt coverage	Expressly included
Formulation coverage	Broad carrier claims; limited formulation detail
Method coverage	Broad antimicrobial and administration-route claims
Manufacturing claims	No manufacturing process claims are provided
Device or delivery claims	None apparent
Current term	Expired
Current blocking power	None

The absence of manufacturing-process claims is significant. A company could design around the disclosed synthetic routes while still evaluating whether its final compound fell within the chemical claims. Conversely, a process claim could have created a separate barrier even after a compound claim became vulnerable. The supplied claims do not show that type of process protection.

What manufacturing and intellectual-property barriers remain?

Patent 4,078,071 does not impose a current manufacturing barrier. A generic or follow-on manufacturer would instead evaluate:

chemical identity and stereochemistry;
salt form;
polymorph or crystalline form;
impurity profile;
API manufacturing route;
residual solvents and elemental impurities;
topical formulation performance;
stability and packaging;
regulatory monograph requirements;
later patents covering a commercial product.

The patent claims do not expressly recite stereochemistry, polymorphism, particle size, release profile, excipient selection, or manufacturing parameters. Those omissions reduce the patent’s relevance to modern formulation and CMC exclusivity analysis.

How does this patent compare with later imidazole antifungal estates?

Patent 4,078,071 is structurally broader than a single-molecule patent but less commercially complete than a modern product estate.

Estate type	Typical protection	Status relative to Patent 4,078,071
Early chemical genus patent	Broad Markush structures	Patent 4,078,071 is representative
Specific compound patent	One active ingredient or salt	Claims 15-28 and 35 approach this model
Formulation patent	Cream, foam, gel, nanoparticle, or delivery system	Not materially developed in the supplied claims
Method patent	Specific infection or regimen	Patent 4,078,071 uses broad antimicrobial methods
Manufacturing patent	Process, catalyst, purification, or solid form	Not apparent from the supplied claims
Regulatory exclusivity	New drug, orphan, pediatric, or clinical exclusivity	Not established by this patent

Competing imidazole antifungals such as clotrimazole, miconazole, econazole, ketoconazole, sulconazole, oxiconazole, tioconazole, and related agents have separate chemical and regulatory histories. Structural similarity alone does not establish that any of those products falls within Patent 4,078,071.

What revenue exposure is associated with Patent 4,078,071?

There is no current direct revenue exposure from the patent itself because the patent expired in 1995. The patent cannot support a present royalty stream, injunction, generic stay, or exclusivity premium.

Historical revenue exposure would require proof that a commercial product practiced one or more asserted claims and that the patent was enforceable during the relevant sales period. The supplied claims do not identify a marketed product, NDA, ANDA, licensee, royalty arrangement, or settlement.

For current investment analysis, the patent should be assigned a zero value as an exclusionary U.S. asset. Its residual value is limited to:

prior-art significance;
freedom-to-operate documentation;
historical licensing analysis;
validity analysis for later patents;
technical understanding of substituted imidazole antifungals.

What claim-construction issues affect infringement analysis?

Several drafting issues require attention.

First, claim 32 identifies R1 as “phenyl” rather than “phenethyl,” which differs from claim 1 and may be a transcription or prosecution-history issue. Second, the claims contain typographical errors, including “akyl,” “therof,” “portozoa,” “chorophenyl,” and “integer.” Third, claims 15 through 28 depend on claim 8, creating a dependency chain that must be read together with the parent limitations. Fourth, claim 35 uses a structural description that should be checked against the patent’s drawing and specification because its chain nomenclature may differ from the corresponding compound in claim 15.

These defects do not revive the patent or create current enforceability. They matter primarily in historical claim interpretation and prior-art analysis.

What is the geographic coverage of the patent estate?

The supplied information establishes only the U.S. patent. U.S. Patent 4,078,071 has no current U.S. term. Patent rights in Europe, Canada, Japan, Australia, or other jurisdictions would depend on separately filed national or regional applications and their individual expiration, lapse, and maintenance records.

A U.S. expiration does not establish foreign expiration. For a present international freedom-to-operate review, the relevant question is whether any later or corresponding foreign patent remains in force in the target market. Patent 4,078,071 itself cannot create foreign rights beyond the jurisdictions in which corresponding applications were granted.

Key Takeaways

U.S. Patent 4,078,071 covers substituted imidazole antimicrobial compounds, salts, compositions, and methods.
The broadest chemical claim is claim 1, a Markush claim covering oxygen- and sulfur-linked aryl imidazole structures.
Claims 15 through 28 and claim 35 identify narrower chlorinated and brominated phenylthio compounds.
Claims 29 through 31 cover antimicrobial compositions, including topical formulations containing approximately 0.1% to 10.0% active compound.
Claims 32 through 34 cover topical, oral, and parenteral antimicrobial methods.
The patent issued in 1978 and expired no later than 1995 under the pre-URAA 17-year term.
It has no current Orange Book blocking value and cannot support a current Paragraph IV stay.
No manufacturing-process, polymorph, device, or modern delivery-system claims are apparent from the supplied claims.
Its remaining commercial relevance is historical and analytical rather than exclusionary.
Later patents covering related imidazole compounds, formulations, manufacturing methods, or dosage forms must be evaluated separately.

FAQs About U.S. Patent 4,078,071

Does Patent 4,078,071 still block generic antifungal products?

No. The patent expired no later than 1995 and does not currently block generic development.

Does the patent cover all imidazole antifungals?

No. It covers a defined structural genus requiring the specified aryl-containing R1 and R2 groups, chain length, and oxygen or sulfur linkage.

Does claim 31 protect every topical antifungal cream?

No. Claim 31 requires a covered compound or salt, a pharmaceutically acceptable carrier, topical use, and an active concentration of approximately 0.1% to 10.0%.

Can the expired patent be used against a later patent application?

Yes. Its disclosure may be relevant prior art against later claims, subject to the later patent’s priority date, statutory framework, claim scope, and disclosure requirements.

Does a salt of a claimed compound receive separate patent protection today?

No. The patent expressly includes antimicrobial acid-addition salts, but that protection expired with the patent. A later salt patent would require its own valid, unexpired claims.

References

United States Patent and Trademark Office. (1978). U.S. Patent No. 4,078,071.
35 U.S.C. §§ 154, 156, 271, 282.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	1622276	⤷ Start Trial
Australia	505298	⤷ Start Trial
Belgium	844516	⤷ Start Trial
Canada	1077493	⤷ Start Trial
Switzerland	621117	⤷ Start Trial
Switzerland	623040	⤷ Start Trial
Switzerland	636089	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,078,071

Summary for Patent: 4,078,071